Structure based drug design efforts aimed at HIV-1 protease inhibition have produced dozens of publically available X-ray crystal structures. This ensemble includes drug resistance mutants, multiple crystal forms, and variation in ligand. The relative importance of these factors, as expressed through structural variance, is being explored. Particularly, we are concerned with the magnitude of variance associated with each variable as well as where the differences are manifest. The relative importance of these structural details are of consequence for rational drug design and for interpreting structural studies on drug resistant mutant proteases.